In a variety of mammalian species, the antinatriuretic and kaliuretic renal components of the physiological response to aldosterone have been demonstrated to be separable effects. These effects may therefore be regulated by distinct and separate sets of biochemical events. From previous work in our laboratories, it has been suggested that the metabolism of aldosterone to polar metabolites of aldosterone is important in the mechanism of action of this hormone. The synthesis of these metabolites and the peak levels they reach in the plasma of rats might account for part of the latent period of the hormone may only be necessary for the regulation of one of these components, particularly the kaliuretic effect. The intention of the current work is to establish further the physiological importance of the large quantities of polar metabolites of aldosterone found in vivo in the kidney, liver, and blood of rats. Following their large scale preparation, isolation and purification, (a) they will be tested in vivo for both their antinatriuretic and/or kaliuretic effects in rats and (b) their chemical structure will be ascertained with the help of mass spectrographic analysis. We have shown that the antinatriuretic and kaliuretic effects of aldosterone in adrenalectomized rats, and the kaliuretic effect in intact rats, are sex-dependent. The metabolism of aldosterone in these rats and the rates of clearance of aldosterone and its metabolites from the plasma via the bile are also sex-dependent. The role of the enterohepatic circulation in the regulation of the levels of aldosterone and its metabolites in vivo will be investigated. The role of the sex hormones and the pituitary on the metabolism of aldosterone and its enterohepatic circulation will also be explored in detail. BIBLIOGRAPHIC REFERENCES: Fecal and Urinary Excretion of 3H-Aldosterone and its Sex Dependence in Rats, D.J. Morris, J.A. Silverman and R. Tsai, J. Steroid Biochem. 7:561, 1976. The Effects of Castration and Treatment with Testosterone on the Biliary Excretion of 3H-Aldosterone in Rats, D.J. Morris and G.A. DeConti, Endocrinology 99:476, 1976.